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Genomic profiling of collaborative cross founder mice infected with respiratory viruses reveals novel transcripts and infection-related strain-specific gene and isoform expression.

Identifieur interne : 001645 ( Main/Exploration ); précédent : 001644; suivant : 001646

Genomic profiling of collaborative cross founder mice infected with respiratory viruses reveals novel transcripts and infection-related strain-specific gene and isoform expression.

Auteurs : Hao Xiong [États-Unis] ; Juliet Morrison [États-Unis] ; Martin T. Ferris [États-Unis] ; Lisa E. Gralinski [États-Unis] ; Alan C. Whitmore [États-Unis] ; Richard Green [États-Unis] ; Matthew J. Thomas [États-Unis] ; Jennifer Tisoncik-Go [États-Unis] ; Gary P. Schroth [États-Unis] ; Fernando Pardo-Manuel De Villena [États-Unis] ; Ralph S. Baric [États-Unis] ; Mark T. Heise [États-Unis] ; Xinxia Peng [États-Unis] ; Michael G. Katze [États-Unis]

Source :

RBID : pubmed:24902603

Descripteurs français

English descriptors

Abstract

Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron-exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.

DOI: 10.1534/g3.114.011759
PubMed: 24902603


Affiliations:


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Le document en format XML

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<term>Animals</term>
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<term>Gene Expression Profiling</term>
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<term>Influenza A virus</term>
<term>Lung (metabolism)</term>
<term>Lung (virology)</term>
<term>Mice</term>
<term>Orthomyxoviridae Infections (genetics)</term>
<term>Orthomyxoviridae Infections (virology)</term>
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<term>Sequence Analysis, RNA</term>
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<term>ARN (génétique)</term>
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<term>Charge virale</term>
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<term>Infections à Orthomyxoviridae (virologie)</term>
<term>Phénotype</term>
<term>Poumon (métabolisme)</term>
<term>Poumon (virologie)</term>
<term>Régulation de l'expression des gènes</term>
<term>Souris</term>
<term>Spécificité d'espèce</term>
<term>Syndrome respiratoire aigu sévère (génétique)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Virus de la grippe A</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>RNA</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Orthomyxoviridae Infections</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>ARN</term>
<term>Infections à Orthomyxoviridae</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Lung</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr">
<term>Infections à Orthomyxoviridae</term>
<term>Poumon</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Lung</term>
<term>Orthomyxoviridae Infections</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Female</term>
<term>Gene Expression Profiling</term>
<term>Gene Expression Regulation</term>
<term>Genome</term>
<term>Influenza A virus</term>
<term>Mice</term>
<term>Phenotype</term>
<term>SARS Virus</term>
<term>Sequence Analysis, RNA</term>
<term>Species Specificity</term>
<term>Viral Load</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Analyse de profil d'expression de gènes</term>
<term>Analyse de séquence d'ARN</term>
<term>Animaux</term>
<term>Charge virale</term>
<term>Femelle</term>
<term>Génome</term>
<term>Phénotype</term>
<term>Régulation de l'expression des gènes</term>
<term>Souris</term>
<term>Spécificité d'espèce</term>
<term>Virus de la grippe A</term>
<term>Virus du SRAS</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron-exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection. </div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>États-Unis</li>
</country>
<region>
<li>Californie</li>
<li>Caroline du Nord</li>
<li>Oregon</li>
</region>
<settlement>
<li>Portland</li>
</settlement>
<orgName>
<li>Université de Washington</li>
</orgName>
</list>
<tree>
<country name="États-Unis">
<region name="Oregon">
<name sortKey="Xiong, Hao" sort="Xiong, Hao" uniqKey="Xiong H" first="Hao" last="Xiong">Hao Xiong</name>
</region>
<name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name>
<name sortKey="Ferris, Martin T" sort="Ferris, Martin T" uniqKey="Ferris M" first="Martin T" last="Ferris">Martin T. Ferris</name>
<name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E" last="Gralinski">Lisa E. Gralinski</name>
<name sortKey="Green, Richard" sort="Green, Richard" uniqKey="Green R" first="Richard" last="Green">Richard Green</name>
<name sortKey="Heise, Mark T" sort="Heise, Mark T" uniqKey="Heise M" first="Mark T" last="Heise">Mark T. Heise</name>
<name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G" last="Katze">Michael G. Katze</name>
<name sortKey="Morrison, Juliet" sort="Morrison, Juliet" uniqKey="Morrison J" first="Juliet" last="Morrison">Juliet Morrison</name>
<name sortKey="Pardo Manuel De Villena, Fernando" sort="Pardo Manuel De Villena, Fernando" uniqKey="Pardo Manuel De Villena F" first="Fernando" last="Pardo-Manuel De Villena">Fernando Pardo-Manuel De Villena</name>
<name sortKey="Peng, Xinxia" sort="Peng, Xinxia" uniqKey="Peng X" first="Xinxia" last="Peng">Xinxia Peng</name>
<name sortKey="Schroth, Gary P" sort="Schroth, Gary P" uniqKey="Schroth G" first="Gary P" last="Schroth">Gary P. Schroth</name>
<name sortKey="Thomas, Matthew J" sort="Thomas, Matthew J" uniqKey="Thomas M" first="Matthew J" last="Thomas">Matthew J. Thomas</name>
<name sortKey="Tisoncik Go, Jennifer" sort="Tisoncik Go, Jennifer" uniqKey="Tisoncik Go J" first="Jennifer" last="Tisoncik-Go">Jennifer Tisoncik-Go</name>
<name sortKey="Whitmore, Alan C" sort="Whitmore, Alan C" uniqKey="Whitmore A" first="Alan C" last="Whitmore">Alan C. Whitmore</name>
</country>
</tree>
</affiliations>
</record>

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